Men with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) experience slower PSA progression if they receive abiraterone plus prednisone first followed by enzalutamide upon PSA progression rather than the opposite sequence, new study findings suggest.

“Our results confirm that second-line enzalutamide is active and should be considered an appropriate treatment option at first progression on abiraterone plus prednisone,” a team led by Kim N. Chi, MD, of the Vancouver Prostate Centre in Vancouver, British Columbia, concluded in a paper published in Lancet Oncology.

The finding is from a randomized open-label phase 2 trial conducted at 6 cancer centers in British Columbia, Canada that enrolled 202 men with newly diagnosed mCRPC. Investigators randomly assigned patients to receive either abiraterone 1000 mg orally once daily plus prednisone 5 mg orally twice daily until PSA progression followed by crossover to enzalutamide 160 mg orally once daily (101 patients, group A) or the opposite sequence (101 patients, group B).

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At the time of data cutoff, 73 patients in group A (72%) and 75 (74%) in group B had crossed over. At a median follow-up of 22.8 months, the time to second PSA progression was significantly longer in group A than group B (median 19.3 vs 15·2 months), Dr Chi’s team reported. Patients in group A had a significant 34% decreased risk of second PSA progression compared with those in group B.

The investigators observed a PSA response (30% or greater decline from baseline) to second-line therapy in 26 (36%) of 73 patients for enzalutamide and 3 (4%) of 75 patients for abiraterone.

“Our trial is the first, to our knowledge, to show an advantage to using a sequencing strategy of both drugs: the treatment sequence of abiraterone plus prednisone followed by enzalutamide had a longer time to PSA progression than did the opposite sequence,” Dr Chi and colleagues wrote.

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The most common grade 3-4 adverse events (AEs) throughout the trial were hypertension, which occurred in 27 (27%) of 101 patients in group A and 18 (18%) of 101 patients in group B, and fatigue, which occurred in 6 (10%) and 4 (4%) of patients, respectively. Serious AEs occurred in 15 (15%) of 101 patients in group A and 20 (20%) of 101 patients in group B. No treatment-related deaths occurred.


Khalaf DJ, Annala M, Taavitsainen S, et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label phase 2, crossover trial. Lancet Oncol. 2019;20:1730-1739.